title: Cholesteryl ester transfer protein and hepatic lipase gene polymorphisms: effects on hepatic mRNA levels, plasma lipids and carotid atherosclerosis.
abstract: OBJECTIVE
  HDL modifying effects of cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) depend in part on each other. We studied associations of CETP-Taq1B and -514C>T-LIPC polymorphisms with hepatic mRNA levels, and their combined effects on plasma lipids and carotid atherosclerosis.
  
  
  METHODS
  We genotyped the CETP-Taq1B and the -514C>T-LIPC polymorphisms in 67 obese women in whom hepatic CETP and LIPC transcript levels were determined as well as in 1549 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR). Carotid atherosclerosis was assessed by intima-media thickness and extent of plaques (B-score) of the carotid arteries.
  
  
  RESULTS
  In obese women, CETP-Taq1B and -514C>T-LIPC variant alleles were associated with reduced hepatic levels of CETP and LIPC mRNA, respectively. The CETP and LIPC polymorphisms accounted for 12.9 and 14.4% of the variability in respective transcripts. In the SAPHIR population, CETP-Taq1B showed independent effects on LDL diameter, HDL and LDL cholesterol, apolipoproteins AI and B and cholesterol/HDL cholesterol, while -514C>T-LIPC revealed independent effects on HDL cholesterol and apolipoprotein AI. The two polymorphisms displayed interactions at the level of HDL cholesterol. Compared to subjects carrying wild-type alleles at both loci, subjects homozygous for the CETP wild-type allele, but heterozygous for the LIPC polymorphism and subjects heterozygous for the CETP polymorphism, but homozygous for the LIPC wild-type allele showed an increased risk of carotid atherosclerosis (both P<0.05).
  
  
  CONCLUSIONS
  CETP and LIPC polymorphisms influence the respective hepatic transcript levels, demonstrate interactions on HDL cholesterol and suggest that imbalances between CETP and LIPC activities may modulate the risk of carotid atherosclerosis.
authors.affiliation: Department of Laboratory Medicine, Paracelsus Medical University, Müllner Hauptstr. 48, 5020 Salzburg, Austria.
authors.forename: Selma M
authors.initials: SM
authors.lastname: Soyal
authors.forename: Anton
authors.initials: A
authors.lastname: Sandhofer
authors.forename: Penelope
authors.initials: P
authors.lastname: Hahne
authors.forename: Hannes
authors.initials: H
authors.lastname: Oberkofler
authors.forename: Thomas
authors.initials: T
authors.lastname: Felder
authors.forename: Bernhard
authors.initials: B
authors.lastname: Iglseder
authors.forename: Karl
authors.initials: K
authors.lastname: Miller
authors.forename: Franz
authors.initials: F
authors.lastname: Krempler
authors.forename: Josef R
authors.initials: JR
authors.lastname: Patsch
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
mesh_terms: D000328:Adult; D000368:Aged; D002340:Carotid Artery Diseases / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D053480:Cholesterol Ester Transfer Proteins; C504173:LIPC protein, human; D008055:Lipids; D008075:Lipoproteins, HDL; D008049:Lipase